A single nucleotide polymorphism in the human BDNF gene (Val66Met) affects memory, and influences Alzheimer's disease and depression vulnerability in a sex-specific manner.
To identify genotypic effects of the BDNF and the ApoE genes on disease progression in preclinical AD, we assessed morphological changes using serial magnetic resonance imaging during the preclinical period of AD in 35 individuals.
In conclusion, val66met polymorphism and BDNF serum level between the three groups and genotype did not significantly affect the serum BDNF level or age, Mini-Mental State Examination score in AD and aMCI.
A total of 1,081 adults without dementia (375 healthy subjects and 706 individuals with mild cognitive impairment) were recruited from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to test the influence of BDNFVal66Met polymorphism on cognitive impairment, brain structure atrophy, and change in the levels of CSF biomarkers.
The degeneration of cholinergic basal forebrain (cBF) neurons in Alzheimer's disease (AD) leads to the cognitive impairment associated with this condition. cBF neurons express the p75 neurotrophin receptor (p75<sup>NTR</sup>), which mediates cell death, and the extracellular domain of p75<sup>NTR</sup> can bind to amyloid beta (Aβ) and promote its degradation.
Common pathophysiological events have been identified in depression and AD, including neuroinflammation with an aberrant Tumor Necrosis Factor-α (TNF-α) signaling, and an impairment of Brain-Derived Neurotrophic Factor (BDNF) and Transforming-Growth-Factor-β1 (TGF-β1) signaling.
These results suggested that an NT-3 polymorphism, rs6332, may significantly influence executive function, reflecting interference performances among patients with mild-stage AD.
In Alzheimer's disease (AD), a single-nucleotide polymorphism in the gene encoding brain-derived neurotrophic factor (BDNF<sub>Val66Met</sub>) is associated with worse impact of primary AD pathology (beta-amyloid, Aβ) on neurodegeneration and cognitive decline, rendering BDNF<sub>Val66Met</sub> an important modulating factor of cognitive impairment in AD.
The BDNFVal66Met polymorphism should be considered as a potential moderator of clinical trial outcomes in current treatment and prevention trials in DIAD and sporadic AD.Ann Neurol 2018;84:424-435.
Among 200 outpatients with dementia and MCI, 146 outpatients with mild AD or A-MCI were recruited and divided into two genotypic groups, valine homozygosity (Val/Val) and methionine (Met) carriers, based on the representative BDNF functional polymorphism Val66Met.
Measures of the BDNF genotype, plasma BDNF, MRI-based hippocampal volume, and memory performance were obtained from the Knight Alzheimer Disease Research Center (ADRC) and the Alzheimer's Disease Neuroimaging Initiative (ADNI).
Val66Met Polymorphism in BDNF Has No Sexual and APOE ε4 Status-Based Dimorphic Effects on Susceptibility to Alzheimer's Disease: Evidence From an Updated Meta-Analysis of Case-Control Studies and High-Throughput Genotyping Cohorts.
Our results clarified the available controversies regarding the role of rs6265 in AD and indicated that BDNF may be a female-specific risk gene for AD.
Conflicting results have been reported as to whether genetic variations (Val66Met and C270T) of the brain-derived neurotrophic factor gene (BDNF) confer susceptibility to Alzheimer's disease (AD).